Intensive induction-sequential chemotherapy with BOP/VIP-B compared with treatment with BEP/EP for poor-prognosis metastatic nonseminomatous germ cell tumor: a Randomized Medical Research Council/European Organization for Research and Treatment of Cancer study.
OBJECTIVE
The aim of this randomized trial was to assess the potential therapeutic advantage of an intensive induction-sequential chemotherapy schedule (bleomycin, vincristine, cisplatin [BOP])/etoposide, ifosfamide, cisplatin, and bleomycin [VIP-B]), compared with a regimen based on bleomycin, etoposide, and cisplatin (BEP) (BEP/etoposide and cisplatin [EP]) for the treatment of patients with poor-prognosis metastatic nonseminomatous germ cell tumors (NSGCTs).


METHODS
Patients had one or more of the following: a retroperitoneal mass > or = 10 cm in diameter; mediastinal or supraclavicular mass > or = 5 cm in diameter; at least 20 lung metastases (any size); liver, bone, or brain metastases; and serum beta human chorionic gonadotropin (betaHCG) > or = 10,000 IU/L or alfa fetoprotein (AFP) > or = 1,000 IU/L. A total of 380 patients were accrued between May 1990 and June 1994 into this joint Medical Research Council (MRC)/European Organization for Research and Treatment of Cancer (EORTC) trial; of these, nine patients were deemed ineligible.


RESULTS
There was no significant difference between the two arms in the proportion of patients who achieved a complete response (CR) with chemotherapy alone, ie, 79 of 185 assessable patients (57%) with BEP/EP and 72 of 186 (54%) with BOP/VIP-B (P = 0.687). With a median follow-up of 3.1 years (maximum, 5.8), a total of 107 patients (28%) had progressive disease. There was no significant difference in time to first disease progression, or failure-free or overall survival between the two arms (P = 0.21, 0.101, and 0.190, respectively). The 1-year failure-free survival rates for BEP/EP and BOP/VIP-B were 60% (95% confidence interval [CI], 53% to 67%) and 53% (95% CI, 47% to 61%). Grade 3 or 4 myelosuppression, febrile neutropenia, and weight loss were more pronounced with BOP/VIP-B than with BEP/EP, and there were more toxic deaths with BOP/VIP-B than BEP/EP (18 [9%] v nine [5%]).


CONCLUSIONS
The intensive BOP/VIP-B therapy was associated with more toxicity, but there was no evidence of an improvement in response rate or survival compared with treatment with BEP/EP.
Kaye
S B
SB
Cancer Research Campaign Department of Medical Oncology, University of Glasgow, Western Infirmary, UK. s.b.kaye@beatson.gla.ac.uk
Mead
G M
GM
Fossa
S
S
Cullen
M
M
deWit
R
R
Bodrogi
I
I
van Groeningen
C
C
Sylvester
R
R
Collette
L
L
Stenning
S
S
De Prijck
L
L
Lallemand
E
E
deMulder
P
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D018450:Disease Progression; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D018237:Germinoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
D001761:Bleomycin; D014750:Vincristine; D005047:Etoposide; D002945:Cisplatin; D007069:Ifosfamide